Erk-5 shares high homology in the amino-terminal kinase domain with Erk1/2. However, the long carboxy-terminal kinase domain makes Erk5 a unique MAP kinase. Erk5 is activated by a variety of extracellular signals. The direct upstream kinase of Erk5 is defined as MEK5. Studies show that Erk5 pathway is involved in proliferation, differentiation, oncogenesis, and development.